浸润性小叶癌的生物标志物特征：多形性与经典亚型、临床病理特征和预后分析。
Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.
机构信息
Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China.
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
出版信息
Breast Cancer Res Treat. 2022 Jul;194(2):279-295. doi: 10.1007/s10549-022-06627-y. Epub 2022 Jun 6.
PURPOSE
To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.
METHODS
A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.
RESULTS
Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67 > 20% tumors (P < 0.05). P-ILCs were subdivided into ER+ (63.1%), HER2+ (21.1%) and TN (15.8%). ER+ P-ILCs were mainly showed trabecular and solid growth patterns. Apocrine and solid features were more strongly associated with HER2+ P-ILCs and TN-P-ILCs, respectively. The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had worse prognosis than the same subtypes in the IDC group, while there was no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC had the worst prognosis. Bone was the most common metastatic site in ER+ P-ILCs and TN-P-ILCs. HER2+ P-ILCs tended to metastasize to the brain and liver. DFS of HER2+ P-ILCs and TN-P-ILCs were worse than that of ER+ P-ILCs. Lacking lobular carcinoma in situ and sTILs ≤ 10% were associated with worse survival of ER+ P-ILCs and TN-P-ILCs, respectively. For HER2+ P-ILCs, Ki-67 > 20% and sTILs ≤ 10% were significant factors for lower DFS.
CONCLUSION
P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.
目的
根据生物标志物谱比较多形性浸润性小叶癌（P-ILC）和经典型浸润性小叶癌（C-ILC）的临床病理特征和预后。
方法
纳入了 2011 年至 2021 年间的 667 例 C-ILC 和 133 例 P-ILC。评估了临床病理特征和间质肿瘤浸润淋巴细胞（sTILs）状态。根据 ER/PR 和 HER2 表达对 P-ILC 进行亚型分类。比较了具有生物标志物亚型的匹配 P-ILC、C-ILC 和浸润性导管癌（IDC）患者的总生存和无病生存（DFS）。
结果
与 C-ILC 相比，P-ILC 肿瘤体积更大、分期更高，ER 阳性率更低，HER2 阳性率更高，三阴性（TN）和 Ki-67＞20%的肿瘤更多（P＜0.05）。P-ILC 分为 ER+（63.1%）、HER2+（21.1%）和 TN（15.8%）亚型。ER+P-ILC 主要呈小梁和实体生长模式。大汗腺和实体特征与 HER2+P-ILC 和 TN-P-ILC 分别更密切相关。每个生物标志物组（ER+、HER2+和 TN）的预后因亚型而异。P-ILC 生物标志物亚型的预后比 IDC 组中相同亚型的预后更差，而 P-ILC 与 C-ILC 对应的亚型之间则无差异。P-ILC 的实体变体预后最差。骨是 ER+P-ILC 和 TN-P-ILC 最常见的转移部位。HER2+P-ILC 倾向于转移到大脑和肝脏。HER2+P-ILC 和 TN-P-ILC 的 DFS 比 ER+P-ILC 更差。缺乏小叶原位癌和 sTILs≤10%与 ER+P-ILC 和 TN-P-ILC 的生存不良相关。对于 HER2+P-ILC，Ki-67＞20%和 sTILs≤10%是 DFS 较低的显著因素。
结论
P-ILC 是 ILC 中的侵袭性亚型。分析具有异质性形态学和生物标志物特征的 P-ILC 的预后因素有助于制定个体化治疗方案。
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